Identification of genetic influences on racial disparities in alcohol-related outcome is a subject of great public health relevance. The neurophysiology component of the Howard University Alcohol Research Center (HUARC) has conducted neurophysiology activities since the initial funding project period of 1997-2003. Howard University joined the Collaborative Study on the Genetics of Alcoholism (COGA) as one of seven sites to explore the major genetic influence on vulnerability to alcoholism through identifying clinical endophenotypes that are associated with alcohol dependence. Neurobehavioral experiments were conducted at HUARC in a well constructed neurophysiology laboratory, which is housed in the Howard University General Clinical Research Center. In the subsequent funding project period (2003-2008), HUARC joined the previous COGA sites as the Interactive Research Group (IRPG) and continued to examine the genetic factors associated with alcohol dependence. The HU IRPG site further developed the EEG-ERP laboratory, which is an addition to the existing molecular neuropharmacology laboratory. As part of this research, the Center incorporated the Indiana Breath Alcohol clamp technique, an innovative mechanism that allows for the study of the effects of alcohol on the brain. Activities in the lab have been conducted under the leadership of Dr. Taylor, Director of HUARC. Dr. Nwulia (PI of this new proposal) is a psychiatrist and an alcohol genetic epidemiologist, who has worked closely with researchers at the HUARC. In 2009, Dr. Nwulia was brought in as a member of the neurophysiology core of the HUARC, and brings unique skills in statistical computing to develop this proposal to enhance the HUARC capacity for biomedical signal processing and integration of behavioral function data for analysis of this candidate gene study. Most recently, a pilot study was conducted to determine the comparative responses to alcohol challenge among Individuals with variations in the ADH1B1 and ADH1B3 alleles. A total of 161 participants enrolled in this study. We have now accumulated extensive amount of genetic, neurophysiologic (including resting, eye tracking and critical tracking tasks EEG) and other neurobehavioral data, which could provide a solid basis to explore physiological markers needed to predict disease risk and serve as traits for molecular genetic and expression studies. This R03 proposal will be utilized over the next two years for the following: to acquire state-of-the-art cross-platform software development tools for modeling and analysis of neuronal functional data under a parallel computing environment, suitable for handling the computational burden of neuroinformatic simulations, and to make developed programs freely- available to the scientific community;to process EEG/ERP data we have recorded so far and conduct a comprehensive analysis of the moderating effects of ADH1B*3 polymorphisms on the relationship between controlled alcohol exposure and neurobehavioral outcomes, indexed by EEG features and subjective responses during alcohol challenge;and to create and maintain a large database of extracted resting and event-related EEG features, and cognitive and behavioral response data, recorded simultaneously with EEG during our recent alcohol clamping, studies to serve as a resource of biobehavioral data of African Americans, who are often under-represented in biomedical studies of behavior. Accomplishment of these goals could lead to a large independent R01 study for development and validation of physiological markers for alcohol disease prognosis and endophenotypes for molecular genetic and expression studies. PUBLIC HEALTH RELEVANCE: The neurophysiology core of Howard University Alcohol Research Center (HUARC) was involved as one of seven sites of the Collaborative Study on the Genetics of Alcoholism (COGA), studying the major genetic influence to alcoholism through identification of clinical endophenotypes of alcohol dependence;and after the completion of COGA grant, HUARC has continued to accumulate extensive amount of genetic, neurophysiologic and neurobehavioral data. The goals of this project are: to acquire state-of-the-art cross-platform software development tools for modeling and analysis of neuronal functional data, under a parallel computing environment, suitable for handling the computational burden of high-dimensional neurophysiological data;to process EEG/ERP data we have recorded so far and conduct a comprehensive analysis of the moderating effects of ADH1B*3 polymorphisms on the relationship between controlled alcohol exposure and neurobehavioral outcomes;and to create and maintain a large database of extracted EEG features, and cognitive and behavioral response data, recorded simultaneously with EEG during our recent alcohol clamping studies, to serve as a resource for biobehavioral information on African Americans, who are often under- represented in biomedical studies. Accomplishment of these goals could lead to a large independent R01 study for development and validation of physiological markers for alcohol disease prognosis and endophenotypes for molecular genetic and expression studies.